A population PK-PD model of YH4808, a novel P-CAB, and intragastric pH that incorporated negative feedback by increased intragastric pH onto the systemic exposure to YH4808.

YH4808 is a novel potassium-competitive acid blocker that is under clinical development to treat patients with gastroesophageal reflux disease and peptic ulcer diseases. In this study, the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of YH4808 were modeled in healthy male volunteers who received a single oral dose of YH4808 at 30, 50, 100, 200, 400, 600, and 800 mg or matching placebo and multiple once-daily oral doses of YH4808 at 100, 200, and 400 mg or matching placebo for 7 days. A population PK-PD model adequately described the time-concentration-effect profiles of YH4808.

Comparison of the pharmacokinetics and pharmacodynamics of YH4808 in healthy subjects for defining an appropriate dosing regimen.

Unlabelled: YH4808 is a novel potassium-competitive acid blocker developed for gastric acid-related disorders. Previous studies indicate its potential to improve symptoms of gastric acid-related disorders. The current study was aimed to find the optimal regimen of YH4808 for night time pH control.

Pharmacokinetics of a New, Once-Daily, Sustained-release Pregabalin Tablet in Healthy Male Volunteers.

Purpose: A new sustained-release (SR) pregabalin formulation (YHD1119) designed for once-daily dosing has recently been developed to improve patient adherence. This study aimed to compare the pharmacokinetics of pregabalin SR and immediate-release (IR) formulations after multiple oral doses and to assess the effect of food on the pharmacokinetic profile of the pregabalin SR formulation after a single dose in healthy individuals.

Methods: Two clinical trials were conducted: a randomized, open-label, multiple-dose, 2-treatment, 2-period crossover study to evaluate the steady-state pharmacokinetic properties of SR treatment (pregabalin SR 300 mg once daily for 3 days) and IR treatment (pregabalin IR 150 mg twice daily for 3 days) under fed conditions and a randomized, open-label, single-dose, 2-treatment, 2-period, crossover study to evaluate the effect of food intake on the pharmacokinetic properties of the pregabalin SR formulation.

A population pharmacokinetic-pharmacodynamic model of YH12852, a highly selective 5-hydroxytryptamine 4 receptor agonist, in healthy subjects and patients with functional constipation.

YH12852, a novel, highly selective 5-hydroxytryptamine 4 (5-HT ) receptor agonist, is currently under development to treat patients with functional constipation. In this study, we aimed to develop a pharmacokinetic (PK)-pharmacodynamic (PD) model that adequately described the time courses of the plasma concentrations of YH12852 and its prokinetic effect as assessed by the Gastric Emptying Breath Test (GEBT) and to predict the prokinetic effect of YH12852 at higher doses through PD simulation. We used the plasma concentrations of YH12852 from patients with functional constipation and healthy subjects and the GEBT results from healthy subjects obtained from a phase I/IIa trial.

YH12852, a Potent and Selective Receptor Agonist of 5-hydroxytryptamine, Increased Gastrointestinal Motility in Healthy Volunteers and Patients With Functional Constipation.

Gastrointestinal (GI) motility disorders are common, decreases quality of life, and imposes a substantial economic burden. YH12852 is a novel agonist of 5-hydroxytryptamine for the treatment of GI motility disorders. This phase I/IIa study assessed the tolerability, pharmacodynamic (PD) and pharmacokinetic (PK) profiles of YH12852.

A physiologically-based pharmacokinetic model adequately predicted the human pharmacokinetic profiles of YH4808, a novel K-competitive acid blocker.

A physiologically-based pharmacokinetic (PBPK) model was developed for YH4808, a novel potassium-competitive acid blocker, using the SimCYP® Simulator based on the physicochemical, in vitro preclinical and clinical data of YH4808. The PBPK model was optimized using YH4808 concentrations obtained from the single-dose phase I clinical trial. Overall, the PBPK model adequately predicted the observed pharmacokinetic profiles of YH4808 in humans.

Effect of food on the pharmacokinetics of YH4808, a potassium-competitive acid blocker, after single- and multiple-oral dosing in healthy subjects.

Purpose: YH4808 is a potassium-competitive acid blocker, developed for the treatment of acid-related disorders. Two clinical studies in healthy male subjects were conducted to evaluate the effect of food on the pharmacokinetics of YH4808.

Methods: The first study, a randomized, three-treatment, three-period, crossover study, compared pharmacokinetics of YH4808 (300 mg) after a single dose at fed state with a standard or a high-fat meal to those at fasted state.

Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

Objective: As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing.

A pharmacokinetic and pharmacodynamic drug interaction between rosuvastatin and valsartan in healthy subjects.

Purpose: Valsartan, an angiotensin-receptor blocker, and rosuvastatin, a competitive inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, are frequently coadministered to treat patients with hypertension and dyslipidemia. The study reported here sought to evaluate the pharmacokinetic and pharmacodynamic interactions between rosuvastatin and valsartan in healthy Korean subjects.

Subjects And Methods: Thirty healthy male Korean subjects were administered with rosuvastatin (20 mg/day), valsartan (160 mg/day), and both drugs concomitantly for 4 days in a randomized, open-label, multiple-dose, three-treatment, three-period crossover study.

Pharmacokinetic interaction between rosuvastatin and telmisartan in healthy Korean male volunteers: a randomized, open-label, two-period, crossover, multiple-dose study.

Purpose: Rosuvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, and telmisartan, an angiotensin receptor blocker, are commonly prescribed in combination for the treatment of dyslipidemia accompanied by hypertension. However, the nature of the pharmacokinetic interaction between the 2 drugs is not clearly understood. The goal of the present study was to investigate the pharmacokinetic drug-drug interaction between rosuvastatin and telmisartan in a healthy Korean population.

Pharmacokinetic interaction between rosuvastatin and metformin in healthy Korean male volunteers: a randomized, open-label, 3-period, crossover, multiple-dose study.

Purpose: Rosuvastatin is indicated for hypercholesterolemia or dyslipidemia and metformin mainly for type 2 diabetes. These 2 drugs are frequently prescribed in combination due to the high comorbidity of the 2 diseases. However the nature of pharmacokinetic interaction between the 2 drugs has not been previously investigated.

Development of a pharmacokinetic interaction model for co-administration of simvastatin and amlodipine.

A model for drug interaction between amlodipine and simvastatin was developed using concentration data obtained from a multiple-dose study consisting of single- and co-administration of amlodipine and simvastatin conducted in healthy Koreans. Amlodipine concentrations were assumed to influence the clearance of simvastatin and simvastatin acid, which as well as the oral bioavailability was allowed to vary depending on genetic polymorphisms of metabolic enzymes. Covariate effects on drug concentrations were also considered.

Bioavailability and tolerability of combination treatment with revaprazan 200 mg + itopride 150 mg: a randomized crossover study in healthy male Korean volunteers.

Background: To date, no definitive treatment of functional dyspepsia (FD) has been proven to be effective and reasonably well-tolerated. Proton pump inhibitors (PPIs) combined with prokinetic agents are considered an effective option. Revaprazan is a selective potassium-competitive acid blocker that reversibly inhibits gastric H(+)/K(+)-ATPase and shows effective acid suppression comparable to PPIs.

Pharmacokinetic comparison of sustained- and immediate-release oral formulations of cilostazol in healthy Korean subjects: a randomized, open-label, 3-part, sequential, 2-period, crossover, single-dose, food-effect, and multiple-dose study.

Background: A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower C(max) and a similar AUC to the immediate-release (IR) formulation.

Objective: The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency.

The effect of beta1-adrenergic receptor gene polymorphism on prolongation of corrected QT interval during endotracheal intubation under sevoflurane anesthesia.

Background: The hemodynamic responses to endotracheal intubation are associated with sympathoadrenal activity. Polymorphisms in the beta1-adrenergic receptor (β(1)AR) gene can alter the pathophysiology of specific diseases. The aim of this study is to investigate whether the Ser49Gly and Arg389Gly polymorphism of the β(1)AR gene have different cardiovascular responses during endotracheal intubation under sevoflurane anesthesia.

Effect of HMGCR variant alleles on low-density lipoprotein cholesterol-lowering response to atorvastatin in healthy Korean subjects.

The investigators quantified the relationship between the genetic polymorphism of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) and the low-density lipoprotein cholesterol (LDL-C)-lowering effects of atorvastatin in a prospective clinical study. Twenty-four healthy participants were grouped into HMGCR rs3846662 GG (n = 13) and AA (n = 11) genotypes and given atorvastatin (20 mg/d) for 14 days. Serum levels of LDL-C, high-density lipoprotein cholesterol, total cholesterol, triglycerides, and creatinine kinase (CK) were measured before (day 1) and 7, 13, 14, 15, 16, 21, and 28 days after dosing initiation.

Modeling the effect of sevoflurane on corrected QT prolongation: a pharmacodynamic analysis.

Background: Sevoflurane may prolong the corrected QT (QTc) interval in healthy humans when administered for induction and maintenance of anesthesia. Little information is available about the dose-response relationship of sevoflurane on the QTc interval. We performed a pharmacodynamic analysis of the relationship between end-tidal sevoflurane concentration (CET) and the QTc.

Effect of CYP2B6 genotype on the pharmacokinetics of sibutramine and active metabolites in healthy subjects.

Sibutramine is a pharmacologic intervention for the treatment of obesity. The effect of CYP2B6 genotypes on the pharmacokinetics of sibutramine and its active metabolites (desmethylsibutramine [M1] and didesmethylsibutramine [M2]) was evaluated in 57 healthy subjects. Each subject received a single oral dose of 10 or 15 mg sibutramine, and blood samples were collected up to 72 hours after dosing.

Pharmacokinetic comparison of controlled-release and immediate-release oral formulations of simvastatin in healthy Korean subjects: a randomized, open-label, parallel-group, single- and multiple-dose study.

Background: A controlled-release (CR) formulation of simvastatin was recently developed in Korea. The formulation is expected to yield a lower C(max) and similar AUC values compared with the immediate-release (IR) formulation.

Objective: The goal of this study was to compare the pharmacokinetics of the new CR formulation and an IR formulation of simvastatin after single- and multiple-dose administration in healthy Korean subjects.

CYP3A5*3 genotype associated with intrasubject pharmacokinetic variation toward tacrolimus in bioequivalence study.

Tacrolimus is metabolized by CYP3A and has highly variable pharmacokinetics. To study the factors contributing to this high variability in pharmacokinetics and to investigate the possibility of genotype-specific clinical applications, the effect of differing CYP3A5 genotypes on the intrasubject coefficients of variation for tacrolimus was investigated. Genotyping for CYP3A5*3 was performed in healthy volunteers who had previously participated in the pharmacokinetic study of 2 tacrolimus formulations with a 2 x 2 cross-over design.